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Biomedical subjects

L Pedneault

Publications and source records attributed to L Pedneault.

At least 19 recordsLinked to original sources
PubMed2001

Recurrent cleft lip and palate in siblings of a patient with malabsorption syndrome, probably caused by hypovitaminosis a associated with folic acid and vitamin B(2) deficiencies.

We present a woman with metabolic disorders secondary to malabsorption and renal disease who gave birth to a stillborn male fetus with left unilateral cleft lip and palate and a live born infant with left unilateral cleft lip and palate. We discuss potential cofactors that could be implicated in the abnormal embryonic process.

Adult↗
PubMed2001

Safety profile and tolerability of amprenavir in patients enrolled in an early access program.

BACKGROUND: The amprenavir (APV) early or expanded access program was designed to provide open-label APV to patients who would potentially receive benefit beyond that expected from currently available protease inhibitors (PIs) and who were at risk of disease progression before the drug's expected time of regulatory approval. OBJECTIVE: This study was conducted as part of an early access program to assess the safety profile and tolerability of APV in adults and children (> or =4 years of age) who were either intolerant to or, in the opinion of the patient's physician, virologically failing a previous PI-containing antiretroviral regimen. Specific CD4+ cell count and viral load limits were not imposed by this early access protocol. METHODS: This open-label, nonrandomized study was conducted at multiple sites throughout the United States. Adults received APV at a dosage of 1200 mg BID. Patients weighing <50 kg received APV at a dosage of 20 mg/kg BID for the solid formulation or 1.5 mL/kg BID for the liquid formulation. RESULTS: A total of 489 physicians registered for this program; 364 (74.4%) enrolled patients. The safety population of 2217 patients (2048 males [92.4%] and 169 females [7.6%] aged 2 to 74 years) received APV for a median duration of 85 days (range, 2-218 days). Patients in the intent-to-treat population (n = 1427) had extensive experience with antiretroviral therapy. Drug-related treatment-emergent adverse events reported in >3% of patients in the safety population were nausea in 279 patients (12.6%), diarrhea in 197 patients (8.9%), rash in 177 patients (8.0%), vomiting in 148 patients (6.7%), and fatigue in 89 patients (4.0%). Adverse events and laboratory test abnormalities were graded for severity on a scale of 1 to 4 in accordance with AIDS Clinical Trials Group guidelines. Grade 3 treatment-emergent abnormal laboratory values regardless of causality occurring in >3% of patients were neutropenia in 69 of 1887 patients (3.7%; grade 3 toxicity = 500-749/mm3) and elevated triglycerides in 80 of 1593 patients (5.0%; grade 3 toxicity = 751-1200 mg/dL). Most common grade 4 treatment-emergent laboratory abnormalities were elevated serum creatine phosphokinase levels in 36 of 1266 patients (2.8%; grade 4 = >6 times upper normal limit), elevated triglycerides in 39 of 1593 patients (2.4%), and neutropenia in 41 of 1887 patients (2.2%). CONCLUSIONS: The results of this large cohort of patients support the data from the phase II/III clinical development program and suggest that APV has an acceptable safety profile and is generally well tolerated when used in combination with other antiretroviral drugs in a heavily treatment-experienced, heterogeneous patient population.

Adolescent↗
PubMed2000

Safety profile and tolerability of amprenavir in the treatment of adult and pediatric patients with HIV infection.

BACKGROUND: Amprenavir (APV) is a new HIV-I protease inhibitor used in combination with other antiretroviral agents for the treatment of HIV-1 infection. OBJECTIVE: The aim of this study was to assess the safety profile and tolerability of APV. METHODS: A review of data from 358 adults enrolled in 2 phase III, randomized, 48-week, controlled studies and from 268 children enrolled in 1 phase II and 1 phase III study was conducted. The adult data were collected between February 25, 1997, and April 1, 1999. Data were collected in children from September 10, 1997, to January 15, 1999; these data were collected before completion of either study. Adults and children who had and had not been treated previously with antiretroviral agents were enrolled. In these studies, APV was used in combination with 2 nucleoside reverse transcriptase inhibitors. RESULTS: The most common drug-related adverse events in patients receiving APV were gastrointestinal events and oral/perioral paresthesia. The majority of adverse events were mild or moderate in intensity, early in onset, and transient. Nausea (27/358 patients, 8%), vomiting (15/358, 4%), rash (11/358, 3%), and diarrhea/loose stools (9/358, 3%) were the most common adverse events associated with treatment discontinuation. Severe laboratory abnormalities possibly related to APV were rare. In children, the nature and frequency of adverse events were similar to those in adults. Metabolic complications were infrequent in APV studies to date; symptoms related to fat redistribution were reported in <3% of patients treated with APV. Lipid or glucose laboratory abnormalities were reported with similar frequency in the APV and control groups in both studies in adults. CONCLUSIONS: In the clinical trials reviewed, APV was generally well tolerated when administered with other antiretroviral agents in adult and pediatric patients with HIV infection.

Adolescent↗
PubMed2000

The relation between baseline HIV drug resistance and response to antiretroviral therapy: re-analysis of retrospective and prospective studies using a standardized data analysis plan.

To assess the relation between resistance to antiretroviral drugs for treatment of HIV-1 infection and virological response to therapy, results from 12 different studies were re-analysed according to a standard data analysis plan. These studies included nine clinical trials and three observational cohorts. The primary end-point in our analyses was virological failure by week 24. Baseline factors that were investigated as predictors of virological failure were plasma HIV-1 RNA, the number and type of new antiretroviral drugs in the regimen, and viral susceptibility to the drugs in the regimen, determined by genotyping or phenotyping methods. These analyses confirmed the importance of both genotypic and phenotypic drug resistance as predictors of virological failure, whether these factors were analysed separately or adjusted for other baseline confounding factors. In most of the re-analysed studies, the odds of virological failure were reduced by about twofold for each additional drug in the regimen to which the patient's virus was sensitive by genotyping methods, and by about two- to threefold for each additional drug that was sensitive by phenotyping.

Anti-HIV Agents↗
PubMed2000

Amprenavir in combination with lamivudine and zidovudine versus lamivudine and zidovudine alone in HIV-1-infected antiretroviral-naive adults. Amprenavir PROAB3001 International Study Team.

OBJECTIVES: To compare the antiviral activity and safety of a new protease inhibitor, amprenavir (141W94) in combination with lamivudine and zidovudine, versus lamivudine and zidovudine alone in HIV-1 infected, antiretroviral-naive subjects. DESIGN: Subjects (n=232) with a CD4 T cell count of > or =200 cells/mm3, plasma HIV-1 RNA levels of > or =10000 copies/ml, and < or =4 weeks of prior nucleoside antiretroviral therapy, were stratified according to baseline plasma HIV-1 RNA level (10000-30000; 30000-100000; or >100000 copies/ml). Subjects received double-blind treatment with either 1200 mg amprenavir twice daily in combination with lamivudine (150 mg twice daily) and zidovudine (300 mg twice daily) (amprenavir/lamivudine/zidovudine) or matched placebo, lamivudine and zidovudine for 16 weeks. Thereafter, subjects with confirmed plasma HIV-1 RNA levels of > or =400 copies/ml could add open-label amprenavir or switch to other antiretrovirals and continue treatment for up to a minimum of 48 weeks. The primary endpoint of the study was defined as the proportion of subjects with plasma HIV-1 RNA of <400 copies/ml at 48 weeks. RESULTS: At 48 weeks, a significantly greater proportion of amprenavir/lamivudine/zidovudine subjects had plasma HIV-1 RNA levels <400 copies/ml than lamivudine/ zidovudine subjects in the overall population: 41 versus 3% (intent-to-treat missing equals failure analysis) (P<0.001); 93 versus 42% (as-treated analysis) (P<0.001); and within each of the three randomization strata (P<0.001). Subjects on amprenavir/lamivudine/zidovudine experienced longer time to event (permanent discontinuation of randomized therapy or viral rebound) than those on lamivudine/zidovudine (median of 33 versus 13 weeks; P<0.001). A significantly greater incidence of drug-related nausea, vomiting, rash and oral/perioral paresthesia was observed with amprenavir/lamivudine/zidovudine than with lamivudine/zidovudine. CONCLUSIONS: Amprenavir, in combination with lamivudine and zidovudine, has potent and durable antiviral activity in antiretroviral-naive subjects over 48 weeks. Amprenavir was safe and generally well tolerated.

Adolescent↗
PubMed1998

Natural history of Epstein-Barr virus infection in a prospective pediatric cohort born to human immunodeficiency virus-infected mothers.

To determine whether Epstein-Barr virus (EBV) constitutes a contributing factor in AIDS and, conversely, whether the human immunodeficiency virus (HIV) alters the course of primary EBV infection in a pediatric population, 62 children born to HIV-infected mothers and prospectively followed were evaluated. EBV infection was documented by EBV-specific serology and polymerase chain reaction and by clinical history. HIV infection status was determined according to the Centers for Disease Control and Prevention pediatric classification system. Demographics from HIV-infected and HIV-uninfected children were comparable. The data suggest that HIV-infected children may acquire primary EBV infection earlier in life. The incidence of accompanying splenomegaly or hepatomegaly (or both) around the time of EBV seroconversion was higher among HIV-infected children than among HIV-uninfected children. In contrast, HIV disease progression and HIV-1 RNA load did not seem to be influenced by primary EBV infection.

AIDS-Related Opportunistic Infections↗
PubMed1998

Intra-assay performance characteristics of five assays for quantification of human immunodeficiency virus type 1 RNA in plasma.

Three kits (Roche AMPLICOR human immunodeficiency virus type 1 [HIV-1] Monitor, Chiron enhanced-sensitivity bDNA, and Organon Teknika NASBA HIV-1 QT) and two in-house assays (from National Genetics Institute and Baylor College of Medicine) were compared with a blinded panel. The results were evaluated as to intra-assay sensitivity, precision, and ability to detect differences in a dilution series.

Evaluation Studies as Topic↗
PubMed1997

Cellular immunity is activated and a TH-2 response is associated with early wheezing in infants after bronchiolitis.

OBJECTIVE: To determine whether abnormalities of cellular immunity are present and linked to early wheezing after bronchiolitis. METHODS: We prospectively studied 26 infants hospitalized for a first episode of bronchiolitis and without any prior immune, cardiac, or respiratory disease. Blood was obtained at the time of enrollment and 5 months later for the assessment of the total cellular and differential counts, CD4+ (helper) and CD8+ (suppressor/cytotoxic) lymphocytes, and the activation markers CD23 (low-affinity immunoglobulin E receptor) and CD25 (interleukin-2 (IL-2) receptor). The cytokines interferon gamma (T-helper (TH) type-1 cytokine) and IL-4 (TH-2) were measured in plasma and in vitro after stimulation with IL-2 or with the house-dust mite (Dermatophagoides farinae) antigen. A daily log of episodes of wheezing was kept by parents after discharge. RESULTS: We found an increase in blood eosinophils, an increased percentage of CD4+, CD25+, and CD23+ lymphocytes in subjects at 5 months compared with the time of bronchiolitis and with healthy subjects of the same age (p < 0.05). Plasma IL-4 levels, although not different from those of healthy subjects, also increased significantly. Peripheral blood lymphocytes from infants who wheezed produced more IL-4 in vitro, 5 months after bronchiolitis, in response to D. farinae antigen. In babies who wheezed, a positive correlation was found between the total number of days that wheezing occurred and the blood eosinophil count. Babies who wheezed more often (> 20 days) had more peripheral blood basophils and eosinophils, and peripheral blood lymphocytes obtained from these subjects at the time of bronchiolitis produced less interferon gamma on stimulation with IL-2. CONCLUSIONS: Bronchiolitis is followed by activation of cellular immunity, and early wheezing in infants is associated with a TH-2 response.

Acute Disease↗
PubMed1996

Unilateral laterothoracic exanthem. A clinicopathologic study of forty-eight patients.

BACKGROUND: Four years ago, we began seeing young children with an unusual, predominantly unilateral, morbilliform and eczematous, self-limited cutaneous eruption. It appeared to correspond to unilateral laterothoracic exanthem (ULE) reported from France and to an eruption described as "a new papular erythema of childhood" in the United States. OBJECTIVE: We conducted a prospective study of ULE to define its clinical evolution, pathology, and therapy. In addition, we performed epidemiologic and microbiologic investigations in an attempt to determine the cause of ULE. METHOD: We studied 48 children with ULE. In some patients, blood, urine, stool, as well as skin biopsy specimens were analyzed. RESULTS: ULE is a morbilliform, eczematous eruption that often begins close to the axilla and spreads to become bilateral, although it usually retains a unilateral predominance. Patients' mean age at onset is 24.3 months, with a female predominance (2:1) and mean duration of 5 weeks, followed by spontaneous resolution that may or may not be improved with topical corticosteroids. It is characterized by a unique eccrine lymphocytic infiltration. Although signs of infection were reported by most patients, no one infectious agent was identified. No significant epidemiologic factor was found. CONCLUSION: ULE, in young children, is a self-limited morbilliform and scarlatiniform eruption that may represent a specific skin reaction to one or more infectious agents.

Administration, Topical↗
PubMed1996

Antibody responses to two Epstein-Barr virus (EBV) nuclear antigens (EBNA-1 and EBNA-2) during EBV primary infection in children born to mothers infected with human immunodeficiency virus.

A variety of antibody response patterns to the latent Epstein-Barr nuclear antigen (EBNA) family have been described in different groups of subjects infected with Epstein-Barr virus (EBV). The purpose of this study was to characterize the immune response to two EBNA proteins, EBNA-1 and EBNA-2, in a population of children who were born to mothers infected with HIV and who underwent EBV seroconversion. Serial serum specimens from 33 children (nine were infected with HIV, and 24 were not infected) were evaluated for the presence of antibodies to EBNA-1 and EBNA-2 by anticomplement immunofluorescence. All the EBNA serology profiles observed for children in our study who were not infected with HIV were consistent with those described for immunocompetent hosts with acute EBV infection, i.e., development of antibodies to EBNA-1, often preceded by the appearance of a humoral immune response to EBNA-2. In contrast, following EBV primary infection in HIV-infected children, antibodies to EBNA-2 arose after antibodies to EBNA-1 and tended to persist. Further studies are needed to investigate the role of EBNA-2 serology as a prognostic marker in HIV-infected children.

Antibodies, Viral↗
PubMed1994

Phenotypic and genotypic characterization of acyclovir-resistant varicella-zoster viruses isolated from persons with AIDS.

Phenotypic and genotypic analyses were done on 17 varicella-zoster virus (VZV) isolates recovered from 10 persons with AIDS (mean CD4 cell count, 16.4/mm3) who had chronic VZV lesions. Eleven acyclovir-resistant isolates were recovered from 10 patients after a mean of 20.1 weeks of therapy. Six susceptible isolates were recovered before acyclovir treatment (n = 1), early during therapy (n = 4; mean time, 4.2 weeks), or after discontinuation of acyclovir (n = 1). Acyclovir-resistant VZV isolates were deficient in thymidine kinase (TK) or induced a TK with altered substrate specificity; all isolates were susceptible to foscarnet. Ten of 11 acyclovir-resistant mutants contained tk gene mutations, including single nucleotide substitutions in highly conserved binding sites (n = 2) as well as nucleotide deletions (n = 4) and insertions (n = 4). These findings suggest that multiple, nonuniform mutations within the tk gene are associated with acyclovir-resistant VZV phenotypes.

AIDS-Related Opportunistic Infections↗
PubMed1994

Validation of respiratory syncytial virus enzyme immunoassay and shell vial assay results.

The Pathfinder respiratory syncytial virus (RSV) enzyme immunoassay (EIA) (Kallestad), the shell vial (SV) technique, and conventional cell culture (CC) were compared for detection of RSV in nasopharyngeal aspirates. We found sensitivities, specificities, and positive and negative predictive values of 58.4, 100, 100, and 68.2%; 80.7, 97.2, 97.0, and 81.9%; and 77.6, 97.2, 96.9, and 79.5% for the CC, EIA, and SV methods, respectively. The SV and EIA techniques were both more sensitive than CC (P < 0.001). Finally, 29 respiratory viruses other than RSV were identified by CC.

Culture Media↗
PubMed1994

Comparison of novel synthetic peptide-based DETECT-RUBELLA enzyme immunoassays with Enzygnost and IMx for detection of rubella-specific immunoglobulin G.

Enzyme immunoassays (EIAs) using synthetic peptides SP-E1 and SP-E1E2 (DETECT-RUBELLA [Bio-Chem]) were compared with two viral lysate-based EIAs (Enzygnost [Behring] and IMx [Abbott]) for the detection of rubella virus-specific immunoglobulin G antibodies. Sensitivities of 94.7, 100, 98.6, and 100% and specificities of 100, 97.4, 100, and 73.7% were found for the SP-E1, SP-E1E2, Enzygnost, and IMx EIAs, respectively.

Antibodies, Viral↗
PubMed1993

Comparison of polymerase chain reaction and standard Southern blotting for the detection of Epstein-Barr virus DNA in various biopsy specimens.

The sensitivity of the polymerase chain reaction (PCR) assay was compared to that of standard Southern blotting (SB) hybridization for detecting the presence of Epstein-Barr virus (EBV) genomes in biopsy samples from 43 patients with a variety of lymphoproliferative disorders. Two pairs of oligonucleotide primers from the first BamHI M and R leftward reading frames (BMLF1 and BRLF1) of EBV were chosen to amplify DNA. The resulting PCR products were analyzed by gel electrophoresis, transfer and hybridization. Restriction enzyme digestion was used to confirm the specificity of the amplified fragment. EBV DNA was found in 38 of 43 patients, as compared with 9 of 43 patients with the Southern technique. No amplified product was detected with other viruses from the Herpes family, nor with human genomic DNA from healthy adults using the same two sets of primers. These results indicate that EBV can be detected in a greater number of lymphoproliferative lesions than previously appreciated. The implications of these findings are discussed.

Adolescent↗
PubMed1993

Comparison of a whole-virus enzyme immunoassay (EIA) with a peptide-based EIA for detecting rubella virus immunoglobulin G antibodies following rubella vaccination.

A total of 250 human serum samples were tested for rubella virus immunoglobulin G antibodies by two enzyme immunoassays (EIAs), one using whole rubella virus antigen and the other based on the use of synthetic peptide antigen. The samples were taken from 125 volunteers before and after their immunization with the RA 27/3 rubella vaccine. This study indicates that a synthetic peptide-based EIA can favorably replace current viral lysate-based EIAs to detect rubella virus antibodies following immunization. Because the synthetic peptide used in this newly developed EIA represents a putative neutralization epitope of the rubella virus, it could also be instrumental in determining rubella immune status and in assessing vaccine program efficiency.

Adult↗